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HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission


During treatment of HIV infection the virus persists in infected cells in a quiescent or ‘latent’ state. If treatment is stopped, then virus rebounds to detectable levels usually within 2–3 weeks. This is thought to occur due to release of infectious virus from a reservoir of long-lived latently infected cells. Reducing the number of latently infected cells should allow a prolonged period of HIV remission without antiviral treatment. A fundamental question is ‘how frequently does infectious virus emerge from the pool of latently infected cells?’, and thus how much would we need to reduce the number of latently infected cells to produce remission? Here we directly estimate the frequency of successful viral reactivation in four independent cohorts of patients undergoing treatment interruption. We find that active infection is initiated on average once every 5–8 days, considerably more slowly than previously thought. This has important implications for how much we need to reduce the number of latent cells in order to produce remission. Whereas previous analyses suggested that we would need to reduce the latent cell number 2000 fold to produce an average one-year remission, we show that reducing the latent cell number by 50–70 fold could achieve this aim.


Vyšlo v časopise: HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005000
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005000

Souhrn

During treatment of HIV infection the virus persists in infected cells in a quiescent or ‘latent’ state. If treatment is stopped, then virus rebounds to detectable levels usually within 2–3 weeks. This is thought to occur due to release of infectious virus from a reservoir of long-lived latently infected cells. Reducing the number of latently infected cells should allow a prolonged period of HIV remission without antiviral treatment. A fundamental question is ‘how frequently does infectious virus emerge from the pool of latently infected cells?’, and thus how much would we need to reduce the number of latently infected cells to produce remission? Here we directly estimate the frequency of successful viral reactivation in four independent cohorts of patients undergoing treatment interruption. We find that active infection is initiated on average once every 5–8 days, considerably more slowly than previously thought. This has important implications for how much we need to reduce the number of latent cells in order to produce remission. Whereas previous analyses suggested that we would need to reduce the latent cell number 2000 fold to produce an average one-year remission, we show that reducing the latent cell number by 50–70 fold could achieve this aim.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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